Stress failure of pulmonary capillaries as a mechanism for exercise induced pulmonary haemorrhage in the horse

Summary Exercise induced pulmonary haemorrhage (EIPH) is a serious problem in the Thoroughbred industry. The condition apparently occurs essentially in all Thoroughbreds in training but the mechanism has proved elusive. There is now strong evidence that the condition is caused by mechanical failure of the walls of the pulmonary capillaries when the pressure inside them rises to very high levels. It is well known that pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently we have shown that the wall stresses are very large when the capillary transmural pressure is raised, and in anesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mmHg and above. The incidence of stress failure is greatly increased at high lung volumes; and many of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. The principal forces acting on the capillary have been analysed. The strength of the thin part of the capillary wall can be attributed to the Type IV collagen in the extracellular matrix. The pulmonary vascular pressures of galloping Thoroughbreds reach very high levels. Mean pulmonary artery and left atrial pressures of up to 120 and 70 mmHg respectively have been directly measured with indwelling catheters. The reason for the high pulmonary vascular pressures is that these animals have been selectively bred over hundreds of years to run at great speeds over short distances and their maximal oxygen consumptions are very high. As a consequence, cardiac outputs are substantial, and the left ventricle needs very high filling pressures. Ultrastructural studies of Thoroughbred lungs after galloping show the typical changes of stress failure of capillaries. Calculations of capillary wall stress from measurements of the radius of the capillaries and the thickness of the wall confirm that the stresses are very high. The fact that the lesions of EIPH are most commonly seen initially in the dorso caudal region of the lung appears to argue against the stress failure hypothesis. However, it is known that resting blood flow is particularly high to that region and it may also be that the alveolar pressure falls transiently to very low levels or that the alveoli in that region are overexpanded. All these factors could increase capillary wall stress. There is evidence that frusemide reduces pulmonary vascular pressures during galloping. However, the blood gas barrier needs to be extremely thin for gas exchange, but immensely strong to withstand the capillary wall stresses. Thoroughbreds fail on both counts. First they develop arterial hypoxaemia as a result of diffusion limited oxygen transfer in the lung during galloping and, therefore, they cannot afford to have thicker blood‐gas barriers. On the other hand, their capillary walls are not strong enough to withstand the substantial wall stresses that develop as a result of the high capillary pressures. Therefore, to some extent, EIPH is an inevitable consequence of the extremely high cardiac outputs required by these elite athletes.